The metabolism of avermectins B1a, H2B1a, and H2B1b by liver microsomes

Drug Metab Dispos. 1982 May-Jun;10(3):268-74.

Abstract

The avermectins area a new class of structurally related antiparasitic agents isolated from Streptomyces avermitilis. The major polar metabolites isolated from in vitro incubations of [3H]avermectins B1a, H2B1a, and H2B1b with either rat or steer liver microsomes have been isolated and identified as the C24-methyl alcohols of the parent compounds. A smaller quantity of a more polar metabolite has also been identified as the monosaccharide of the C24-methyl alcohols of avermectin H2H1b from rat liver microsomal incubation and avermectin H2B1a from steer liver microsomal incubation. The mass spectra and 300-MHz 1H-NMR spectra permitted assignment of structures to these metabolites. Together these two metabolites represent 50-80% of the total radioactivity more polar than the parent compounds. The metabolite profiles on reverse-phase HPLC demonstrate that the rat and steer are qualitatively similar in the production of these two polar metabolites.

MeSH terms

  • Animals
  • Antiprotozoal Agents / metabolism*
  • Cattle
  • Chemical Phenomena
  • Chemistry
  • Chromatography, High Pressure Liquid
  • In Vitro Techniques
  • Ivermectin
  • Lactones / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes, Liver / metabolism*
  • Rats

Substances

  • Antiprotozoal Agents
  • Lactones
  • avermectin H2B1b
  • avermectin B(1)a
  • Ivermectin
  • avermectin